The parasitic trematode Schistosoma mansoni exhibits a complicated life cycle involving obligate mammalian and molluscan hosts. Widespread infection with S. mansoni is responsible for major human health problems in tropical countries. Advances in understanding this disease are restricted by the complex biology of the organism, limited availability and expense of material for study, and lack of some experimental approaches fruitful in other fields. In particular, in vitro cell culture and nucleic acid transfection techniques would provide an effective complement to existing approaches. We have developed cell culture conditions that allow survival and limited proliferation of cells from juvenile worms and sporocysts of S. mansoni, representative of cells from the two life cycle stages. It is our goal to establish indefinitely proliferating cell lines and use them in studies relevant to treatment and prevention of schistosomiasis. For this work we take approaches analogous to those producing established cell lines from other organisms. These include: (1) medium formulation to satisfy the biochemical and biological requirements of the cells; (2) genetic alteration to generate cells with simplified and less regulated proliferative requirements, and (3) alternate passaging of cells in vivo and in vitro as a means to rescue and expand a small population of cells with indefinite growth potential. Once we have derived a homogeneous population of proliferating cells, we will attempt transfection of the cultures with exogenous DNA. Development of cell lines and transfection techniques will allow new approaches in molecular biology, nutrition, physiology, endocrinology, immunology, and pharmacology of this parasite and provide an accessible source of parasite material for laboratories that do not have facilities to maintain the complex life cycle of the organism. our approaches also may be applicable to in vitro culture of cells from other lower invertebrates. These applications may provide additional experimental tools in nonmammalian models of developmental biology, neurobiology and other basic biological disciplines that are relevant to biomedical research in general. We are particularly interested in pursuing the use of S. mansoni cell lines as potential vaccines, as experimental models for drug screening and genetics of drug resistance, and in the study of hormonal signalling mechanisms in these parasites.